The compound 2-chloro-11-(4-methyl-1-piperazinyl)-dibenz[ b,f][1,4]oxazepine is a known compound having therapeutic effects on the central nervous system. U.S. Pat. No. 3,546,226 specifically discloses 2-chloro-11-(4-methyl-1-piperazinyl)-dibenz[b,f][1,4]oxazepine, its nontoxic pharamaceutically acceptable acid addition salts, their parenteral administration and their utility as central nervous system agents. U.S. Pat. 3,663,696 discloses a parenteral solution composed of 2-chloro-11-(1-piperazinyl)-dibenz[ b,f][1,4]oxazepine and certain acid addition salts thereof, in a mixture of propylene glycol, water and ascorbic acid. U.S. Pat. No. 3,412,193 discloses the oral administration of 2-chloro-11-(4-methyl-1-piperazinyl)-dibenz[b,f][1,4]-oxazepine in propylene glycol for the purpose of testing anti-fertility efficacy.
Problems have existed with preparations containing 2-chloro-11-(4-methyl-1-piperazinyl)-dibenz[b,f][1,4]oxazepine. Due to the compound's low solubility in water, it is difficult to formulate in conventional pharmaceutical forms such as parenteral and oral liquid preparations employing, for example, water for injection. Another problem which makes the compound difficult to prepare in liquid dosage forms in its low solubility in liquids having a basic or near neutral pH. A still further problem associated with the compounds is that one of its hydrolysis products, namely, 2-chloro-dibenz[b,f][1,4]oxazepin-11(10H)-one, is extremely insoluable in water. Aqueous solutions of 2-chloro-11-(4-methyl-1-piperazinyl)-dibenz[b,f][1,4]oxazepine have proven unstable and unsuitable primarily because of the precipitation of the above hydrolysis product which forms in trace amounts long before the potency of the solution has dropped below acceptable levels. Although the hydrolysis product is nontoxic, its precipitation is, of course, unacceptable in an injectable solution of the active oxazepine. All of the above problems can be overcome by the application of the instant invention.
The oxazepine of this invention and its acid addition salts can be prepared as illustrated in U.S. Pat. No. 3,663,696.